The overall objective of this Superfund Basic Research Program Project on toxic metals is to understand the human health impact of exposure to arsenic and mercury from environmental and anthropogenic sources. This program consists of three biomedical and two non-biomedical research projects, two scientific support cores, and an Administrative, Research Translation and Training Core. Projects 2 (Hamilton) and 8 (Stanton) are molecular toxicology projects investigating the molecular mechanisms by which arsenic elicits its adverse health effects, focusing on endocrine disruption and disruption of membrane protein trafficking and function, respectively. Project 7 (Chen) is an ecotoxicology project examining how mercury bioaccumulates in fish, and Project 9 is a plant biology project focusing on bioaccumulation of arsenic in rice, each focusing on how these lead to human exposures of concern. Project 4 (Karagas) is examining the human health effects of exposure to arsenic and mercury, focusing on reproductive and developmental effects in offspring of pregnant women in New Hampshire who are exposed to these toxicants via their food (arsenic and mercury) and well water (arsenic). Core B (Jackson) is a Trace Elements Analysis Core that provides state-of-the-art ultra-low level detection, quantitation and speciation of arsenic and mercury. Core E (Moore) is an Integrative Biology Core that provides comprehensive support and integration of knowledge from the project-specific molecular biology, genomics, proteomics, bioinformatics, biostatistics and modeling analysis (each provided by individual cores at Dartmouth) to the program in order to more fully understand, integrate and translate this knowledge to stakeholders. The investigators'Research Translation Core is designed to effectively facilitate this translation by assisting them in communicating the proper information in the most effective and appropriate way to each stakeholder group. The Training Core is designed to exploit their highly interdisciplinary and collaborative program in order to foster the most effective training of their students. The goal is to provide the very best science that can be used for more effective science-based risk assessments, for predicting the specific patho-physiological consequences of arsenic and mercury exposure, for assessing gene-environment, agent-agent and other complex environmental interactions, for assessing specifically sensitive sub-populations at elevated risk, and for developing effective interventions for these exposed populations.